Stories

Lighting Up Brain Tumor Tissue

People like you help turn a gee-whiz idea into a tool that promises to improve surgical outcomes for kids with brain tumors.

Published in Connection magazine, Spring 2017

It was 2004 and Dr. Jim Olson, an oncologist at Seattle Children’s, hoped that surgery had gone well for one of his patients, a 16-year-old girl with an aggressive brain tumor. Olson felt confident. After all, Dr. Rich Ellenbogen, one of the best pediatric neurosurgeons in the nation, had performed the operation that had lasted all day and into the evening. But when Olson and Ellenbogen looked at a post-operative MRI scan of the teen’s brain, they were devastated to still see a big piece of cancerous tumor – tissue that had the potential to take her life.

The two agreed that they needed a better way to guide surgeons in the painstaking process of distinguishing healthy tissue from cancerous and benign tumors (any solid lump of cells in the brain can be life-threatening). Challenging Olson to go back to his lab at Fred Hutch and find a way, Ellenbogen even asked him if he could make the tumor cells light up as a visual marker. “We committed to finding a solution,” remembers Olson. “But we had no idea how we were going to do it.”

Bridging the funding gap

What he landed on sounded like science fiction. Olson thought the ideal approach was to use a fluorescent dye like the one that illuminated blood vessels during vascular surgeries, but he needed it to cross the blood-brain barrier and specifically bind to tumor and not healthy brain tissue. So he attached the dye to a “carrier” molecule found in the venom of a scorpion species known as the deathstalker. The molecule transports the scorpion’s venom through its prey’s system to its brain. He found it worked in mice too: When injected into the body, the molecule goes to the brain and naturally binds to tumor cells so the dye can illuminate them.

Olson dubbed his invention “tumor paint” and tried repeatedly to get federal grants to continue his early research. Though he had data that showed its ability to light up brain tumors in lab mice, the scientists who were part of the confidential peer review process rejected his grant applications several times.

“Reviewers thought it would never work in humans or we’d never finish the work in the amount of time allocated for the grant,” explains Olson. “Support from donors bridged this funding gap, allowing us to accelerate our research and move tumor paint closer to the finish line.”

Fueling an inventive idea

Tumor paint inventor Dr. Jim Olson (right) shows off a tattoo of chlorotoxin – the scorpion molecule that is part of tumor paint – to Jana Lindeman, whose guild raises money to help further Olson’s research.

Jana Lindeman is on a mission. In 1996, she lost her 5-year-old daughter, Jordyn Dukelow, to a brain tumor. Even though surgeons were able to remove 90% of the baseball-sized mass, the tumor grew back. A few years later, Lindeman’s friends formed the first fundraising guild at Seattle Children’s dedicated to raising money for research – specifically, research to improve treatments for brain tumors.

“Dr. Olson came to one of our guild meetings to talk about tumor paint,” remembers Lindeman. “All I could think was, ‘how fast can we get this into surgeon’s hands so that other children will benefit?’”

At least half of the funding that supported tumor paint’s development in the lab came from money raised by guilds like the one dedicated to Jordyn. From selling handmade greeting cards and registering runners for 5K races to holding chili cook-offs, guild efforts helped Olson generate the data he needed to get to the next step.

Pushing science forward

Dr. Sarah Leary, an oncologist at Seattle Children’s, designs and leads clinical trials that determine which new therapies will improve outcomes for kids with brain tumors.

Oncologist Dr. Sarah Leary designed and is leading the clinical research trial to see if tumor paint can successfully work in kids. It’s the first pediatric clinical trial for tumor paint in the world.

To date, about 20 children have received tumor paint at Seattle Children’s as part of a phase 1 clinical trial, which tests the drug’s safety and determines optimal dose. So far, tumor paint has passed safety testing with flying colors.

When Leary invited Laura Coffman to enroll her 2-year-old son Hunter in the phase 1 trial, Coffman’s knee-jerk reaction was a firm “no thank you.” But after talking more with Leary, Coffman decided she couldn’t be scared about testing a new tool to treat brain tumors.

Today, the golf ball-sized tumor next to Hunter’s brain stem is gone and Coffman is a strong advocate for brain tumor research. “Funding means research, research means cures and cures mean more kids’ lives are saved,” she says.

After the phase 1 trial closes this summer, Leary will lead a national clinical trial in the fall to test tumor paint’s effectiveness at lighting up brain tumor tissue for surgeons. The multi-site trial will enroll children at 15 of the leading pediatric brain tumor centers in the United States. Leary’s team at Seattle Children’s will be in charge of reviewing all tumor images and tissue samples.

70: Number of new brain tumor cases at Seattle Children’s annually

“At the end of the national clinical trial, we’ll be able to say how well tumor paint works for pediatric brain tumor patients,” says Leary. “We’ll also have additional safety information, which will be a huge step towards making tumor paint a standard part of neurosurgical care for children.”

Supporting great promise

Dr. Amy Lee is the lead neurosurgeon for the tumor paint clinical trials at Seattle Children’s.

Dr. Amy Lee, who is the lead neurosurgeon for the tumor paint trials at Seattle Children’s, believes tumor paint has great potential to be an effective tool for surgeons. One thing she’s sure of: Tumor paint will never replace a surgeon’s judgment.

“Even when tumor paint lights up tumor tissue, that doesn’t necessarily mean we can take the tumor out safely,” explains Lee. “Sometimes we have to leave tumor tissue in sensitive areas of the brain so we don’t affect a child’s function or cause paralysis. The hope is that chemotherapy and radiation will take care of any tumor we have to leave behind.”

Lee is particularly excited to try out a new device for the surgical microscope being developed and built for the national trial. The new instrument – funded by the Norcliffe Foundation – will feature two lights: one that illuminates the tumor paint and makes tumor cells fluoresce, and one that lights up the surgical area inside the brain. Surgeons will be able to toggle back and forth between the two lights so they can see tumor tissue light up and then take it out while protecting critical areas of the brain.

“It was not a hard decision for our family foundation to fund the new surgical devices,” says Nora Kenway, a Norcliffe board member and a longtime Seattle Children’s donor whose teen son Andrew died from a brain tumor in 2001. “This trial is an important step forward in the critical work to develop better treatments for brain tumors. It’s a blessing for surgeons to have another tool to be able to employ in the fight to save a child’s life.”

Stepping up for science

Liesel Von Imhof, 17, arrived at Seattle Children’s from her home in Anchorage after an MRI revealed the reason for her migraines: a ping-pong ball–sized tumor in the middle of her brain that was blocking the drainage of spinal fluid.

“Dr. Leary came into my room and talked to us about participating in the tumor paint trial,” remembers Liesel. “My mom didn’t want me to do anything on top of the standard surgery because she was so scared, but I said ‘This is groundbreaking medical science and I’ll be part of history. How cool would that be?’”

In the end, Liesel’s parents left the decision up to her and she took part in the trial. Liesel knew the trial was testing the drug’s safety and that her surgeons weren’t using it to distinguish tumor from healthy tissue. But even still, when she and her mom heard that the round lump of tumor Ellenbogen and Lee had removed from the deepest part of her brain was glowing when it was placed under the special tumor paint light, they were both glad she’d played a role in tumor paint’s journey to become a tool available to all surgeons.

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